1. Field of the Invention
The present invention relates to particle/polymer composites and more specifically, the present invention relates to particle/polymer combinations (wherein the particles are diamonds or oxides) and methods for making the composites for use in applications inside or outside the human body.
2. Background for the Invention
There is a continuous search for biocompatible materials suitable for fabrication of soft, flexible components of biomedical devices implantable inside the human body (e.g., artificial joints, such as hips and knees, artificial heart valves, catheters, valves for drainage of saline form the eye to treat the glaucoma condition, breast implants, and more) or located externally to, but in contact with the biological environment of the human body (e.g., soft contact lenses).
BioMEMS Devices for Drainage of Eye Liquid:
Materials currently used to fabricate implantable devices suffer from adhesion of proteins, and therefore the development of fibrosis, which leads to heightened immune response.
Microelectromechanical system (MEMS) valves have been developed to drain liquid from the eye to reduce the abnormal intraocular pressure increase due to the pathological condition known as glaucoma. Glaucoma is a gradual increase, sometimes rapid, in the internal pressure of the liquid in the eye. Glaucoma occurs when natural drainage tubes become clogged due to biological processes. Resulting high pressure leads to destruction of the cells and the optic nerve responsible for signal transmission to the brain for image formation. The increase in the eye's pressure is a high-risk condition that affects about 67 million people in the world resulting in impaired vision up to blindness, if not properly treated.
Currently there are drug and surgical treatments available to lower the intraocular pressure. In cases when the drug or surgery treatment do not work, the alternative is to insert implants in the eye (“shunts”), which feature passive valves to drain the excess liquid that produce over-pressure, via micro-tubes, as disclosed in Patent No. W099/66871. This patent describes a device about 1 cm long—implantable in the eye to decrease the ocular pressure, via a safety valve that regulates the liquid pressure, once the latter exceeds the value that affects the eye health. However, current implants have problems, as discussed below:                The dimensions of the implants are not small enough and the material cannot avoid fibrosis, due to attachment of proteins to the surface of the device.        Surgery does not optimize the intraocular pressure nor make it predictable, resulting in hipotonia or high resistance to liquid flow.        The intraocular pressure change during the day, and that carination cannot be compensated by passive valves.        The hydrophilic nature of the surface of polymers currently used in MEMS valves leads to protein or cells attachment to the surface, thus immune rejection.        
Attempts have been made recently to replace passive valves by active micro-valves actuated chemically or electromagnetically using MEMS technology. In this respect, Byunghoon J. Micromech. Microeng 13 (2003) 613 described an ocular implant to control glaucoma via an electromagnetically actuated membrane moved by magnetic force. The membrane is made of an elastic polymer of low Young's modulus.
Alternatively, U.S. Pat. No. 6,168,575 (Soltanpour et al.) describes a small pump (5-15 mm long) implantable in the eye to remove excess fluid to automatically control the eye pressure. Control is achieved via a pressure sensor connected to a microprocessor and positioned outside the eye. The patent referenced above discusses the disadvantages of automatic adjustment in relation to muscular hipotony.
U.S. Pat. No. 6,589,203 describes a device implantable in the eye, which includes a deformable surface of a material capable of resisting continuous deformation. The device also features a tube, with a valve sensitive to pressure variation, to drain the eye liquid.
U.S. Pat. No. 6,682,500 awarded to Soltanpour et al. describes a device with a diaphragm pump made of a synthetic metal-based polymer. This device has two valves, one in the tube at the entrance to the pump and the other at the exit to regulate the fluid flow.
Unfortunately, all implants described above exhibit biocompatibility and dimension problems, which result in malfunction and liquid flow obstruction. Significant challenges include making surfaces of the polymer based microtube bioinert.
U.S. Pat. No. 7,127,286 discloses a device with electronic circuitry formed on silicon and then uniformly covered with ultra-nanocrystalline diamond (UNCD) for implantation inside the eye, on the retina, to restore sight to people blinded by retina photoreceptor degeneration. However, care must be taken in producing this device as the UNCD film needs to be grown at about 400-450° C. These temperatures often destroy the Si chip during encapsulation, depending on the amount of time needed to grow a hermetic UNCD film. In addition, the UNCD film does not exhibit the high insulation needed to induce leakage currents≦9×10−9 A/cm2, while the Si microchip is powered inside the eye.
BioMEMS for Drug Delivery:
An intractable problem is the administration of drugs to patients in a safe, efficient way. Typical drug carriers are chemical vehicles, which more recently are combined with nanoparticles such as nanocapsules, nanospheres, and polymer matrices. (Vautier et al. 2007). None of the current drug delivery approaches involve inert components, or active, controllable and predictable systems. This results in uncontrolled, more expensive, and riskier (secondary effects) drug delivery devices due to lack of control over drug release mechanisms.
Recently, several groups have been investigating and developing microchips with integrated microelectromechanical/nanoelectromechanical (MEMS/NEMS) devices for intelligent, efficient, reduced cost and safer drug delivery. Although some prototype devices have been demonstrated for application to pathologies like osteoporosis and delivery of vasopresin for soldiers in the battle field, there are still problems, particularly on biocompatibility of the devices.
Typically, implants invoke the formation of a fibrous capsule and these leads to a response from biological tissue in the form of local inflammation. Extraction of the implanted device usually follows. Implant rejection inhibits the normal function of the device, when for example, fibrosis prevents sensors from having access to analyte. Also, drug-delivery devices encounter a barrier to deliver the drug.
Several approaches have been investigated to reduce or eliminate the fibrous capsule, such as encapsulation with polymers (PEG), surface texturing in the device material, and production of porous membranes to minimize the adhesion of cells.
These approaches have problems, such as lack of active control and adhesion issues of the materials (polymers) due to temperature changes. Use of packaging may be a solution, but it appears costly and also the materials used for packaging exhibit biocompatibility problems themselves, in addition to lacking active control.
In the drug delivery field, microchips control drug delivery. These systems involve MEMS-based reservoirs on a Si wafer, which are covered by a membrane electrically actuated or activated by remote RF communication to release the drugs in the reservoir. All the devices mentioned above are fabricated with materials like Si, which are not biocompatible, or polymers that are partially biocompatible, since after some time of implantation they elicit body reactions as described above.
Artificial Joints:
The joints of the human body generally have two opposing surfaces in movable, repetitive contact with each other, and as such are biological rollers. Prostheses (manmade mechanical rollers) are used to replace these worn out biological rollers. The surfaces of the components of the prosthesis slide one-upon-each other while wetted by naturally occurring synovial fluid. Thus, the combination of the prosthesis motion and the lubricating synovial fluid controls the performance of the joint.
Natural joint surfaces exhibit characteristics that are difficult to reproduce. For example, cartilage regenerates and also has the ability to soften impacts. Currently, the materials used in the fabrication of artificial joints do not exhibit all of the characteristics of natural joints.
There is a search for prosthesis materials (mechanical roller) with very low coefficient of friction (COF) and wear. However, the material currently used for fabrication of prosthesis release particles when they are sliding one-upon-each other, and those particles lead to problems either because eliciting adverse reactions from the human body, due to inferior biocompatible character of the particles organism or because they generate undesirable ions.
Research and development of prosthesis materials have focused on four material pairs, all of which have advantages and disadvantages, namely: 1) Metal/Polyethylene, 2) Metal/Metal, 3) Ceramic/Ceramic and Metal/Ceramic. Ceramic/Ceramic exhibits the lowest wear. However, because ceramic materials are brittle, they risk fracture.
Metal/metal pairs exhibit low wear, but their use results in the production of metal ions. These particles, emitted from the worn metal surfaces are small and numerous.
Metal/Polyethylene pairs exhibit the highest wear, compared to the other two pairs, thus the prosthesis fabricated with this pair have a short lifetime. Neutron and electron irradiation of metal and polyethylene couples increase their resistance to wear, but at the cost of becoming more fragile.
Metal/Ceramic pairs exhibit superior properties to Metal/Metal pair in terms of friction and wear rates. Metal/ceramic configurations also exhibit comparable properties to the three other candidates in terms of range of motion (ROM). This prosthesis pair provides acceptable lifetimes when implanted in people of relatively advanced age, does not provide acceptable lifetimes when implanted in younger people.
A September 2011 report from the National Joint Registry for England and Wales, revealed that failure rates of metal-on-metal hips, such as the DePuy ASR and certain Pinnacle devices are increasing. Generally research has focused on developing materials with low coefficient of friction and low wear rates for prostheses. Low COF and wear-rate coatings also are being explored, as hard materials exhibit less wear than soft materials. Materials such as titanium nitride and carbons have been investigated as coatings. However, these materials have problems of adhesion, resulting in delamination from the base material of the prosthesis.
It is generally known that hips are the most replaced joints, and that research on new materials for hips is leading the effort on the development of prosthesis. However, replacement of knees is becoming also a frequent event, and currently knee replacements are reaching numbers similar to those of hips. Knees are subject to more stringent motions and thus exhibit shorter lifetimes than the hips.
Polymer-Based Implants:
A myriad of attempts have been made to incorporate polymers into implant devices. FIG. 1 is a picture of a valve for implantation in the eye to minimize pressure associated with glaucoma. However, protein adhesion to polymers exacerbates the body's rejection of such systems. FIG. 2 is a photograph of the device depicted in FIG. 1, but with protein adhesion on the surface (fibrosis), Coating of the silicone glaucoma valve with a UNCD layer eliminates the protein attachment (fibrosis) FIG. 4. shows the absence of such adhesions.
FIG. 4 is a photograph of a silicone-based glaucoma valve body, which was coated with a UNCD film prior to implantation into a rabbit eye. The device is shown in pristine condition, even after five months of implantation. No evidence of fibrosis is found on this UNCD-coated polymer construct.
Another example of a device based on a polymer platform, this one located externally to, but in contact with the biological environment of the human body, is a soft contact lens. Such lenses exhibit the problem of protein adhesion to the surface, which reduces the lifetime of the lens, and requires frequent cleaning.
Silicone elastomers (a particular kind of polymer) have been widely used for coating cardiac pacemakers, as platform material for implantable catheters and mammary prostheses. The use of silicone has been particularly extensive in the fabrication of mammary prostheses. However, despite the relative inertness of silicone elastomers, they still elicit inflammatory or reign body reaction in many patients to different degrees. This reaction is induced when a foreign body enters into the human tissue, which responds by surrounding the foreign substance with a sheath of fibrous tissues to render the foreign substance harmless. However, the fibrosis induced by the non-very biological material results in scar-type tissue. The fibrous capsule formed around the implant can contract and becomes hard and rigid, resulting in substantial discomfort, and ultimately in failure of the implant.
Encapsulating the polymer with a bioinert film is a possible solution to solve the aforementioned protein adhesion problems. However, often the coating process results in an unwanted hardening of the polymer. For example, using a UNCD film to cover the surface of the polymer requires that the construct be heated to 400-450° C. This results in hardening (loss of the natural flexibility) of the polymer.
In addition, coating of the polymer surface with a UNCD layer requires a time consuming seeding process, embedding nanodiamond particles on the surface by exposure of the polymer to a ultrasonic bath featuring a solution of nanodiamond particles in a solvent like methanol, followed by several hours of growth of the UNCD layer in a microwave plasma chemical vapor deposition (MPCVD) system featuring an Ar/CH4 gas mixture-based plasma.
There is a need in the art for a process for producing substrates having reduced coefficients of friction and improved strength. The process should be compatible with existing manufacturing processes. The resulting substrates should be biocompatible and less susceptible to attack by immune systems and chemical moieties generally.